Potential new weapon in TB drug arsenal

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The first promising tuberculosis (TB) drug in almost 40 years could be the most potent yet and also treat the disease faster, according to research published online yesterday (9 December) by Science Express.

The research team, led by Koen Andries, found that the new drug R207910 works by blocking an enzyme the bacterium uses to acquire energy. Because earlier drugs did not target this enzyme specifically, the researchers say the new drug could even be used against strains of the TB bacterium — Mycobacterium tuberculosis — that are resistant to existing drugs.

About two million people die from the disease every year, according to the World Health Organization (WHO). Chris Dye at the WHO's Stop TB Partnership says, "The neglect in TB drug development is due partly to the fact that TB was thought, in the Western world, to be a disease of the past".

"Investment in drug discovery has also been low because the market is in the poorest parts of the world," says Dye. "TB patients are mostly poor people who cannot afford to pay for costly treatments developed by major drug companies."

But recently the profile of TB has been raised dramatically because of the growing problem of TB and HIV co-infection, says Mel Spigelman, director of research and development at the Global Alliance for Tuberculosis Drug Development.

According to the organisation — created in 2000 to push for more research into TB drugs — 12 million people worldwide have both diseases. Most of them live in southern Africa.

About two-thirds of people with TB do not have access to effective treatment. Even when they receive treatment, says Dye, the drugs fail to work against resistant strains.

WHO's recommended DOTS (Directly Observed Treatment, Short Course) strategy to fight TB has come under criticism as being out of date (see WHO's TB strategy comes under fire) because it requires a long course of treatment (six to eight months) and constant monitoring and assessment.

Marcos Espinal, one of Dye's colleagues, told SciDev.Net that speed — both in treatment and in developing new drugs — is crucial. "A faster and simpler therapy for TB is critical to accelerate current TB control efforts and ultimately eliminate this major killer".

Dye agrees that the ability to shorten the duration of treatment to about two months would be "a big step forward for TB control, with benefits both for patients and health services".

A new drug would also need to be low-cost to compete with current anti-TB drugs priced at about US$10 per treatment course, adds Dye.

Andries and colleagues say the new drug would probably be used in combination because the use of one drug on its own has in the past quickly led to drug resistance. When the researchers replaced one of the drugs that make up the current cocktail of TB therapy with R207910, they found that it boosted the effectiveness of existing combination treatments.

The effectiveness of R207910 has been tested only in mice so far. The drug passed safety tests in healthy people, but the next step will be to investigate how effective it is when used to treat people with full-blown TB.

Several other TB drugs are in development, says Spigelman. But, he adds, whether R207910 is used together with other novel drugs or in a mix of old and new drugs will probably depend on how the different combinations work when tested in clinical trials in people.